A synthetic peptide based on a glycine-gated chloride channel induces a novel chloride conductance in isolated epithelial cells

CK4-M2GlyR, an aqueous soluble peptide derived from the transmembrane M2 se gment of the glycine-gated Cl- channel found in postsynaptic membranes of t he central nervous system, has previously been shown to increase transepith elial Cl- and fluid secretion of epithelial monolayers. The goal of this st udy was to determine whether CK4-M2GlyR exerts these effects via formation of a novel chloride conductance pathway, modulation of endogenous chloride channel activity, or a combination of these effects. Ionic currents were re corded from isolated epithelial cells before and after treatment with the p eptide using the whole-cell configuration of the patch-clamp technique. CK4 -M2GlyR increased whole-cell Cl- currents in all epithelial cell lines that were studied, including: Madin-Darby canine kidney cells, a human colonic epithelial cell line (T84), and airway epithelial cells derived from a huma n cystic fibrosis patient (IB3-1). No evidence was found for modulation of endogenous Cl- channels by CK4-M2GlyR based on both the electrophysiologica l properties of the observed currents and the pharmacological profile of th e CK4-M2GlyR-induced current. These results suggest that CK4-M2GlyR increas es Cl- permeability in epithelial cells directly, by forming a distinct con duction pathway in cell membranes. (C) 2000 Elsevier Science B.V. All right s reserved.